Recognition of Bacteria and Bacterial Products by Host Immune Cells in Sepsis

  • J. Pugin
Part of the Yearbook of Intensive Care and Emergency Medicine book series (YEARBOOK, volume 1996)


Bacterial sepsis is the leading cause of death in non-coronary intensive care units, and accounts for over 200000 deaths per year in the United States of America [1]. In critically ill patients with a suspected or a proven source of infection, sepsis is characterized by physiological disturbances such as fever or hypothermia, tachycardia, tachypnea, leukocytosis or leukopenia [2, 3]. Severe sepsis is defined by the same condition with evidence of organ dysfunction. Patients in septic shock meet the criteria of severe sepsis with in addition presence of hypotension refractory to volume loading [2]. The condition of physiological disturbances such as in sepsis, but in the absence of infection, is known as “systemic inflammatory response syndrome” (SIRS) [4]. These new definitions of sepsis and related infectious syndromes in critically ill patients underline the trend towards a pathogenic definition of these conditions. Indeed, those definitions reflect the will of clinicians to recenter the disease on host responses, rather than on the triggering infectious microorganism. This is supported by clinical and basic researchers who also recently realized that the pathogenesis of bacterial sepsis depended on host responses rather than on the infectious process [5]. It has recently become clear that bacterial infections initiate host responses through activation of biochemical and cellular cascades, leading to the production of effector immune cells and of endogenous mediators [1, 6, 7]. This response is often adequate and necessary for a rapid immune response directed against the invading microorganism. However, in some cases, this response is inadequate and deleterious for the host himself, and causes the syndrome known as severe sepsis.


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  1. 1.
    Bone RC (1991) Gram-negative sepsis. Chest 100: 802–808PubMedCrossRefGoogle Scholar
  2. 2.
    Bone RC (1991) Let’s agree on terminology. Definitions of sepsis. Crit Care Med 19: 973–976PubMedCrossRefGoogle Scholar
  3. 3.
    Brun-Buisson C, Doyon F, Carlet J, et al (1995) Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. JAMA 274: 968–974PubMedCrossRefGoogle Scholar
  4. 4.
    Bone RC (1992) Toward an epidemiology and natural history of SIRS. JAMA 268: 3452–3455PubMedCrossRefGoogle Scholar
  5. 5.
    Pugin J (1994) Bacteremia, sepsis and shock. Intensive Care Med 20: 92–93PubMedCrossRefGoogle Scholar
  6. 6.
    Glauser MP, Zanetti G, Baumgartner JD, Cohen J (1991) Septic shock: Pathogenesis. Lancet 338: 732–739PubMedCrossRefGoogle Scholar
  7. 7.
    Pugin J, Ulevitch RJ, Tobias PS (1995) Mechanisms of cellular activation by endotoxin. In: Tellado JM, Forse RA, Solomkin JS (eds) Modulation of the inflammatory response in severe sepsis. Karger, Basel. Vol. 20, pp 8–17Google Scholar
  8. 8.
    Thomas L (1974) The life of a cell: Notes of a biology watcherGoogle Scholar
  9. 9.
    Ulevitch RJ, Johnston AR, Weinstein DB (1979) New function for high density lipoproteins. I. Their participation in intravascular reactions of bacteriallipopolysaccharides. J Clin Invest 64: 1516–1524PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Ulevitch RJ, Johnston AR, Weinstein DB (1981) New function for high density lipoproteins. II. Isolation and characterization of a bacterial lipopolysaccharide-high density lipoprotein complex formed in rabbit plasma. J Clin Invest 67: 827–837PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Cavaillon JM, Haeffner-Cavaillon N (1985) The role of serum in interleukin-1 production by human monocytes activated by endotoxins and their polysaccharide moieties. Immunol Letters 10: 35–41CrossRefGoogle Scholar
  12. 12.
    Tobias PS, Soldau K, Ulevitch RJ (1986) Isolation of a lipopolysaccharide-binding acute phase reactant from rabbit serum. J Exp Med. 164: 777–793PubMedCrossRefGoogle Scholar
  13. 13.
    Ramadori G, Meyer zum Buschenfelde KH, Tobias PS, Mathison JC, Ulevitch RJ (1990) Biosynthesis of lipopolysaccharide-binding protein in rabbit hepatocytes. Pathobiology 58: 89–94PubMedCrossRefGoogle Scholar
  14. 14.
    Su GL, Freeswick PD, Geller DA, et al (1994) Molecular cloning, characterization, and tissue distribution of rat lipopolysaccharide binding protein. Evidence for extrahepatic expression. J Immunol 153: 743PubMedGoogle Scholar
  15. 15.
    Wong HR, Pitt BR, Su GL, et al (1995) Induction of lipopolysaccharide-binding protein gene expression in cultured rat pulmonary artery smooth muscle cells by interleukin-1β. Am J Respir Cell Mol Biol 12: 449–454PubMedCrossRefGoogle Scholar
  16. 16.
    Tobias PS, Mathison J, Mintz D, et al (1992) Participation of lipopolysaccharide-binding protein in lipopolysaccharide-dependent macrophage activation. Am J Respir Cell Mol Biol 7: 239–245PubMedCrossRefGoogle Scholar
  17. 17.
    Grube BJ, Cochane CG, Ye RD, et al (1994) Lipopolysaccharide binding protein expression in primary human hepatocytes and HepG2 hepatoma cells. J Biol Chem 269: 8477–8482PubMedGoogle Scholar
  18. 18.
    Tobias PS, Soldau K, Ulevitch RJ (1989) Identification of a Lipid A binding site in the acute phase reactant lipopolysaccharide binding protein. J Biol Chem 264: 10867–10871PubMedGoogle Scholar
  19. 19.
    Schumann RR, Leong SR, Flaggs GW, et al (1990) Structure and function of lipopolysaccharide binding protein. Science 249: 1429–1431PubMedCrossRefGoogle Scholar
  20. 20.
    Weiss J, Elsbach P, Shu C, et al (1992) Human bactericidal/permeability-increasing protein and a recombinant NH2-terminal fragment cause killing of serum-resistant gramnegative bacteria in whole blood and inhibit tumor necrosis factor release induced by the bacteria. J Clin Invest 90: 1122–1130PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Weiss J, Elsbach P, Olsson I, Odeberg H (1978) Purification and characterization of a potent bactericidal and membrane active protein from the granules of human polymorphonuclear leukocytes. J Biol Chem 253: 2664–2672PubMedGoogle Scholar
  22. 22.
    Tobias PS, Mathison JC, Ulevitch RJ (1988) A family of lipopolysaccharide binding proteins involved in responses to gram-negative sepsis. J Biol Chem 263: 13479–13481PubMedGoogle Scholar
  23. 23.
    Heumann D, Gallay P, Betz-Corradin S, Barras C, Baumgartner JD, Glauser MP (1993) Competition between bactericidal/permeability-increasing protein and lipopolysaccharide binding to monocytes. J Infect Dis 167: 1351–1357PubMedCrossRefGoogle Scholar
  24. 24.
    Wright SD, Tobias PS, Ulevitch RJ, Ramos RA (1989) Lipopolysaccharide (LPS)-binding protein opsonizes LPS-bearing particles for recognition by a novel receptor on macrophages. J Exp Med 170: 1231–1241PubMedCrossRefGoogle Scholar
  25. 25.
    Tobias PS, Soldau K, Gegner JA, Mintz D, Ulevitch RJ (1995) Lipopolysaccharide binding protein-mediated complexation of lipopolysaccharide with soluble CDI4. J Biol Chern 270: 10482–10488CrossRefGoogle Scholar
  26. 26.
    Gegner JA, Ulevitch RJ, Tobias PS (1995) Lipopolysaccharide (LPS) signal transduction and clearance: Dual roles for LPS binding protein and membrane CD14. J Biol Chem 270: 5320–5325PubMedCrossRefGoogle Scholar
  27. 27.
    Hailman E, Lichenstein HS, Wurfel MM, et al (1994) Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14. J Exp Med 179: 269–277PubMedCrossRefGoogle Scholar
  28. 28.
    Wurfel MM, Kunitake ST, Lichenstein H, Kane JP, Wright SD (1994) Lipopolysaccharide (LPS)-binding protein is carried on lipoproteins and acts as a cofactor in the neutralization of LPS. J Exp Med 180: 1025–1035PubMedCrossRefGoogle Scholar
  29. 29.
    Ulevitch RJ, Tobias PS (1994) Recognition of endotoxin by cells leading to transmembrane signaling. Curr Opin Immunol 6: 125–130PubMedCrossRefGoogle Scholar
  30. 30.
    Gallay P, Jongeneel CV, Barras C, et al (1993) Short-time exposure to lipopolysaccharide is sufficient to activate human monocytes. J Immunol 150: 5086–5093PubMedGoogle Scholar
  31. 31.
    Wurfel MM, Hailman E, Wright SD (1995) Soluble CD14 acts as a shuttle in the neutralization of lipopolysaccharide (LPS) by LPS-binding protein and reconstituted high density lipoprotein. J Exp Med 181: 1743–1754PubMedCrossRefGoogle Scholar
  32. 32.
    Martin TR, Mathison JC, Tobias PS, Maunder RJ, Ulevitch RJ (1992) Lipopolysaccharide-binding protein enhances the responsiveness of alveolar macrophages to bacterial lipopolysaccharide: Implication for cytokine production in normal and injured lungs. J Clin Invest 90: 2209–2219PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Kitchens RL, Ulevitch RJ, Munford RS (1992) Lipopolysaccharide (LPS) partial structures inhibit responses to LPS in a human macrophage cell line without inhibiting LPS uptake by a CD14-mediated pathway. J Exp Med 176: 485–494PubMedCrossRefGoogle Scholar
  34. 34.
    Wright SD, Ramos RA, Tobias PS, Mathison IC (1990) CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS-binding protein. Science 24: 1431–1433CrossRefGoogle Scholar
  35. 35.
    Gallay P, Heumann D, Le Roy D, Barras C, Glauser MP (1993) Lipopolysaccharidebinding protein as a major plasma protein responsible for endotoxemic shock. Proc Natl Acad Sci USA 1993: 9935–9938CrossRefGoogle Scholar
  36. 36.
    Bazil V, Baudys M, Hilgert I, et al (1989) Structural relationship between the soluble and membrane-bound forms of human monocyte surface glycoprotein CDI4. Mol Immunol 26: 657–662PubMedCrossRefGoogle Scholar
  37. 37.
    Ferrero E, Goyert SM (1988) Nucleotide sequence of the gene encoding the monocyte differentiation antigen, CDI4. Nucleic Acids Res 16: 4173PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Haziot A, Chen C, Ferrero E, Low MG, Silbert R, Goyert SM (1988) The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage. J Immunol 141: 547–552PubMedGoogle Scholar
  39. 39.
    Simmons DL, Tan S, Tenen DG, Nicholson-Weller A, Seed B (1989) Monocyte antigen CD14 is a phospholipid anchored membrane protein. Blood 73: 284–289PubMedGoogle Scholar
  40. 40.
    Weingarten R, Mathison JC, Omidi S, et al (1993) Neutrophils express and up regulate surface antigen CD14 in whole blood. J Leukoc Biol 53: 518–524PubMedGoogle Scholar
  41. 41.
    Iida M, Hirai K, Shinohara S, et al (1994) Lipopolysaccharide primes human basophils for enhanced mediator release: Requirement for plasma co-factor and CDI4. Biochem Biophys Res Commun 203: 1295–1301PubMedCrossRefGoogle Scholar
  42. 42.
    Ziegler-Heitbrock HWL, Pechumer H, Petersmann I, et al (1994) CD14 is expressed and functional in human B cells. Eur J Immunol 24: 1937–1940PubMedCrossRefGoogle Scholar
  43. 43.
    Bazil V, Horejsi V, Baudys M, et al (1986) Biochemical characterization of a soluble form of the 53-kDa monocyte surface antigen. Eur J Immunol 16: 1583–1589PubMedCrossRefGoogle Scholar
  44. 44.
    Martin TR, Rubenfeld G, Steinberg KP, et al (1994) Endotoxin, endotoxin-binding protein, and soluble CD 14 are present in bronchoalveolar lavage fluid of patients with adult respiratory distress syndrome. Chest 105: 55S-56SPubMedCrossRefGoogle Scholar
  45. 45.
    Matsuura K, Setoguchi M, Nasu N, et al (1989) Nucleotide and amino acid sequences of the mouse CD14 gene. Nucleic Acids Res 17: 2132PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Tobias PS, Soldau K, Kline L, et al (1993) Cross-linking of lipopolysaccharide (LPS) to CD14 on THP-1 cells mediated by LPS-binding protein. J Immunol 150: 3011–3021PubMedGoogle Scholar
  47. 47.
    Pugin J, Schürer-Maly CC, Leturcq D, Moriarty A, Ulevitch RJ, Tobias PS (1993) Lipopolysaccharide activation of human endothelial and epithelial cells is mediated by lipopolysaccharide-binding protein and soluble CD14. Proc Natl Acad Sci USA 90: 2744–2748PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Kirkland TN, Finley F, Leturcqu D, et al (1993) Analysis of lipopolysaccharide binding by CD14. J Biol Chem 268: 24818–24823PubMedGoogle Scholar
  49. 49.
    McGinley MD, Narhi LO, Kelley MJ, et al (1995) CD14: Physical properties and identification of an exposed site that is protected by lipopolysaccharide. J Biol Chem 270: 5213–5218PubMedCrossRefGoogle Scholar
  50. 50.
    Juan TS, Hallman E, Kelley MJ, Wright SD, Lichenstein HS (1995) Identification of a domain in soluble CD14 essential for lipopolysaccharide (LPS) signaling but not LPS binding. J Biol Chem 270: 17237–17242PubMedCrossRefGoogle Scholar
  51. 51.
    Juan TS, Kelley MJ, Johnson DA, et al (1995) Soluble CD14 truncated at amino acid 152 binds lipopolysaccharide (LPS) and enables cellular response to LPS. J Biol Chem 270: 1382–1387PubMedCrossRefGoogle Scholar
  52. 52.
    Viriyakosol S, Kirkland TN (1995) A region of human CD14 required for lipopolysaccharide binding. J Biol Chem 270: 361–368PubMedCrossRefGoogle Scholar
  53. 53.
    Lee JD, Kato K, Tobias PS, Kirkland TN, Ulevitch RJ (1992) Trapsfection of CD14 into 70Z/3 cells dramatically enhances the sensitivity to complexes of lipopolysaccharide (LPS) and LPS-binding protein. J Exp Med 175: 1697–1705PubMedCrossRefGoogle Scholar
  54. 54.
    Haziot A, Ferrero E, Lin X, Stewart C, Goyert SM (1994) CD14-negative mice: Anaylsis of the response to LPS. J. Endotoxin Res 1 (Suppl): C136 (Abst)Google Scholar
  55. 55.
    Pugin J, Ulevitch RJ, Tobias PS (1993) A critical role for monocytes and CD14 in endotoxin -induced endothelial cell activation. J Exp Med 178: 2193–2200PubMedCrossRefGoogle Scholar
  56. 56.
    Duchow J, Marchant A, Crusiaux A, et al (1993) Impaired phagocyte responses to lipopolysaccharide in paroxysmal nocturnal hemoglobinuria. Infect Immunol 61 : 4280–4285Google Scholar
  57. 57.
    Beekhuizen H, Blokland I, Corsèl-van Tilburg AJ, Koning F, van Furth R (1991) CD14 contributes to the adherence of human monocytes to cytokine-stimulated endothelial cells. J Immunol 147: 3761–3767PubMedGoogle Scholar
  58. 58.
    Beekhuizen H, van Furth R (1993) Monocyte adherence to human vascular endothelium. J Leukoc Biol 54: 363–378PubMedGoogle Scholar
  59. 59.
    Lee JD, Kravchenko V, Kirkland TN, et al (1993) Glycosyl-phosphatidylinositol-anchored or integral membrane forms of CD14 mediate identical cellular responses to endotoxin. Proc Natl Acad Sci USA 90: 9930–9934PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Weinstein SL, June CH, DeFranco AL (1993) Lipopolysaccharide-induced protein tyrosine phosphorylation in human macrophages is mediated by CD14. J Immunol 151: 3829–3838PubMedGoogle Scholar
  61. 61.
    Han J, Lee JD, Tobias PS, Ulevitch RJ (1993) Endotoxin induces rapid protein tyrosine phosphorylation in 70Z/3 cells expressing CD14. J Biol Chem 268: 25009–25014PubMedGoogle Scholar
  62. 62.
    Han J, Lee JD, Bibbs L, Ulevitch RJ (1994) A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science 265: 808–811PubMedCrossRefGoogle Scholar
  63. 63.
    Lee JC, Laydon JT, McDonnell PC, et al (1994) A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 372: 739–746PubMedCrossRefGoogle Scholar
  64. 64.
    Raingeaud J, Gupta S, Rogers JS, et al (1995) Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. J Biol Chem 270: 7420–7426PubMedCrossRefGoogle Scholar
  65. 65.
    Derijard B, Raingeaud J, Barrett T, et al (1995) Independent human MAP kinase signal transduction pathways defined by MEK and MKK isoforms. Science 267: 682–685PubMedCrossRefGoogle Scholar
  66. 66.
    Cordle SR, Donald R, Read MA, Hawiger J (1993) Lipopolysaccharide induces phosphorylation of MAD3 and activation of c-rel and related NF-ΚB proteins in human monocytic THP-1 cells. J Biol Chem 268: 11803–11810PubMedGoogle Scholar
  67. 67.
    Delude RL, Fenton MJ, Savedra R, et al (1994) CD14-mediated translocation of nuclear factor-κB induced by lipopolysaccharide does not require tyrosine kinase activity. J Biol Chem 269: 22 253–22 260Google Scholar
  68. 68.
    Endo S, Inada K, Kasai T, et al (1994) Soluble CD14 (sCD14) levels in patients with multiple organ failure (MOF). Res Comm Chern Path Pharmacol 84: 17–25Google Scholar
  69. 69.
    Fearns C, Kravchenko V, Ulevitch RJ, Loskutoff DJ (1994) Murine CD14 gene expression in vivo: Extramyeloid synthesis and regulation by lipopolysaccharide. J Exp Med 181: 857–866CrossRefGoogle Scholar
  70. 70.
    Jack RS, Grunwald U, Stelter F, Workalemahu G, Schütt C (1995) Both membranebound and soluble forms of CD14 bind to gram-negative bacteria. Eur J Immunol 25: 1436–1441PubMedCrossRefGoogle Scholar
  71. 71.
    Krüger C, Schütt C, Obertacke U, et al (1991) Serum CD14 levels in polytraumatized and severely burned patients. J Exp Immunol 85: 297–301CrossRefGoogle Scholar
  72. 72.
    Goldblum SE, Brann TW, Ding X, Pugin J, Tobias PS (1994) Lipopolysaccharide (LPS)binding protein and soluble CD14 function as accessory molecules for LPS-induced changes in endothelial barrier function, in vitro. J Clin Invest 93: 692–702PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Arditi M, Zhou J, Dorio R, Rong GW, Goyert SM, Kim KS (1993) Endotoxin-mediated endothelial cell injury and activation: Role of soluble CD14. Infect Immunol 61: 3149–3156Google Scholar
  74. 74.
    Frey EA, Miller DS, Jahr TG, et al (1992) Soluble CD14 participates in the response of cells to lipopolysaccharide. J Exp Med 176: 1665–1671PubMedCrossRefGoogle Scholar
  75. 75.
    Haziot A, Rong G-W, Silver J, Goyert SM (1993) Recombinant soluble CD14 mediates the activation of endothelial cells by lipopolysaccharide. J Immunol 151: 1500–1507PubMedGoogle Scholar
  76. 76.
    Von Asmuth EJU, Dentener MA, Bazil V, Bouma MG, Leeuwenberg JFM, Buurman WA (1993) Anti-CD14 antibodies reduce responses of cultured human endothelial cells to endotoxin. Immunology 80: 78–83Google Scholar
  77. 77.
    Read MA, Cordle SR, Veach RA, Carlisle CD, Hawiger J (1993) Cell-free pool of CD14 mediates activation of transcription factor NF--κB by lipopolysaccharide in human endothelial cells. Proc Nat! Acad Sci USA 90: 9887–9891PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Meyrick BO, Ryan US, Brigham KL (1986) Direct effects of E. coli endotoxin on structure and permeability of pulmonary endothelial monolayers and the endothelial layer of intimal explants. Am J Pathol 122: 140–151PubMedPubMedCentralGoogle Scholar
  79. 79.
    Patrick D, Betts J, Frey EA, Prameya R, Dorovini-Zis K, Finlay BB (1992) Haemophilus influenzae lipopolysaccharide disrupts confluent monolayers of bovine brain endothelial cells via a serum-dependent cytotoxic pathway. J Infect Dis 165: 865–872PubMedCrossRefGoogle Scholar
  80. 80.
    Schletter J, Brade H, Brade L, et al (1995) Binding of lipopolysaccharide (LPS) to an 80-kilodalton membrane protein of human cells is mediated by soluble CD14 and LPSbinding protein. Infect Immunol 63: 2576–2580Google Scholar
  81. 81.
    Haziot A, Rong GW, Lin XY, Silver J, Goyert SM (1995) Recombinant soluble CD14 prevents mortality in mice treated with endotoxin (lipopolysaccharide). J Immunol 154: 6529–6532PubMedGoogle Scholar
  82. 82.
    Haziot A, Rong GW, Bazil V, Silver J, Goyert SM (1994) Recombinant soluble CD14 inhibits LPS-induced tumor necrosis factor-α production by cells in whole blood. J Immunol 152: 5868PubMedGoogle Scholar
  83. 83.
    Grunwald U, Krüger C, Schütt C (1993) Endotoxin-neutralizing capacity of soluble CD14 is a highly conserved specific function. Circ Shock 39: 220–225PubMedGoogle Scholar
  84. 84.
    Pugin J, Ulevitch RJ, Tobias PS (1995) Tumor necrosis factor-α and interleukin-1β mediate human endothelial cell activation in blood at low endotoxin concentrations. J Inflamm 45: 49–55PubMedGoogle Scholar
  85. 85.
    Bone RC (1994) Gram-positive organisms and sepsis. Arch Intern Med 154: 26–34PubMedCrossRefGoogle Scholar
  86. 86.
    Pugin J, Heumann D, Tomasz A, et al (1994) CD14 is a pattern recognition receptor. Immunity 1: 509–516PubMedCrossRefGoogle Scholar
  87. 87.
    Zhang Y, Doerfler M, Lee TC, Guillemin B, Rom WN (1993) Mechanisms of stimulation of interleukin-1β and tumor necrosis factor-α by Mycobacterium tuberculosis components. J Clin Invest 91: 2076–2083PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Espevik T, Otterlei M, Skjak-Braek G, Ryan L, Wright SD, Sundan A (1993) The involvement of CD14 in stimulation of cytokine production by uronic acid polymers. Eur J Immunol 23: 255–261PubMedCrossRefGoogle Scholar
  89. 89.
    Otterlei M, Sundan A, Skjak-Braek G, Ryan L, Smidrod O, Espevik T (1993) Similar mechanisms of action of defined polysaccharides and lipopolysaccharides: Characterization of binding and tumor necrosis factor alpha induction. Infect Immunol 61: 1917–1925Google Scholar
  90. 90.
    Newman SL, Chaturvedi S, Klein BS (1995) The WI-1 antigen of Blastomyces dermatitidis yeasts mediates binding to human macrophage CD11b/CD18 (CR3) and CD14. J Immunol 154: 753–761PubMedGoogle Scholar
  91. 91.
    Weidemann B, Brade H, Rietschel ET, et al (1994) Soluble peptidoglycan-induced monokine production can be blocked by anti-CD14 monoclonal antibodies and by lipid A partial structures. Infect Immunol 62: 4709–4715Google Scholar
  92. 92.
    Opal SM (1995) Clinical trials of novel therapeutic agents: Why did we fail? In: Vincent JL (ed) Yearbook in Intensive Care and Emergency Medicine. Springer Verlag, Berlin, pp 425–436CrossRefGoogle Scholar
  93. 93.
    Ooi CE, Weiss J, Doerfler ME, Elsbach P (1991) Endotoxin-neutralizing properties of the 25 kD N-terminal fragment and a newly isolated 30 kD C-terminal fragment of the 55–60 kD bactericidal/permeability-increasing protein of human neutrophils. J Exp Med 174: 649–655PubMedCrossRefGoogle Scholar
  94. 94.
    Han J, Mathison JC, Ulevitch RJ, Tobias PS (1994) Lipopolysaccharide (LPS) binding protein, truncated at Ile-197, binds LPS, but does not transfer LPS to CD14. J Biol Chem 269: 8172–8175PubMedGoogle Scholar
  95. 95.
    Gallay P, Heumann D, Le Roy D, Barras C, Glauser MP (1994) Mode of action of antilipopolysaccharide-binding protein antibodies for prevention of endotoxemic shock in mice. Proc Natl Acad Sci USA 91: 7922–7926PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Abraham E, Raffin TA (1994) Sepsis clincial trials: Continued disappointment or reason for hope? JAMA 271: 1876–1878PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1996

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  • J. Pugin

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